# The Biology and Biochemistry of ADAR RNA editing enzymes

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $35,980

## Abstract

Project Summary/Abstract
Adenosine Deaminases that act on RNA (ADARs) are a family of RNA editing enzymes that convert
adenosines to inosines in double-stranded RNA (dsRNA). ADARs are essential in mammals and required for
the health of all animals. An important function of ADARs is to target codons to allow a single mRNA to give
rise to multiple protein isoforms. Surprisingly, in all studied organisms, recoding editing sites are rare compared
to the extensive, non-selective, editing that occurs in noncoding regions of mRNAs, such as introns and
untranslated regions. The functions of non-selective editing are unknown, and the proposed research will
capitalize on technological advances, such as RNAseq and CRISPR protocols, to fill this gap in knowledge.
Studies will utilize the model organism C. elegans, since non-selective editing may be solely responsible for
phenotypes of C. elegans lacking ADARs. Experiments will test a model whereby non-selective editing
precludes Dicer processing of dsRNA, thus regulating gene silencing in a developmental and tissue-specific
manner. Studies are facilitated by the genome-wide identification of Editing-Enriched Regions (EERs), which
define the non-selectively edited "dsRNAome". RNAseq analyses will define expression of EER-associated
genes, and endogenous siRNAs (endo-siRNAs) matching these genes, to reveal genes that are good
candidates for ADAR regulation of gene silencing. Deletion of the EER with CRISPR protocols will allow
confirmation that ADAR regulation depends on the presence of the EER. Endo-siRNAs aligning to EERs have
features of direct Dicer products, a species of small RNA not previously observed among C. elegans endo-
siRNAs. Factors involved in the biogenesis of, and silencing by, this newly identified class of endo-siRNAs will
be identified with a screen using a C. elegans strain expressing a GFP reporter that is silenced in an ADAR
mutant strain. Proposed studies will yield strains that lack double-stranded EER(s) in specific genes, and
ADAR mutant strains with additional deletions in factors that rescue ADAR-regulated silencing. These strains
will be tested for their ability to rescue phenotypes of C. elegans lacking ADARs. While correlation of a
phenotype to a specific gene will be a priority, a degron protocol will provide an alternate strategy. Studies are
designed to provide long-awaited details about the functions of C. elegans ADARs, and pave the way for
defining similarities and differences in roles of non-selective editing in other organisms.

## Key facts

- **NIH application ID:** 10048767
- **Project number:** 3R01GM044073-24S1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Brenda L. Bass
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $35,980
- **Award type:** 3
- **Project period:** 1990-04-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10048767

## Citation

> US National Institutes of Health, RePORTER application 10048767, The Biology and Biochemistry of ADAR RNA editing enzymes (3R01GM044073-24S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10048767. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*